We propose to compare the molecular properties of the RNA genomes of two endogenous C-type viruses of the C57BL/Ka mouse. One of these, the radiation leukemia virus (RadLV), is consistently extractable from radiation-induced thymic lymphomas of this strain and is highly leukemogenic, whereas the other, designated BL/Ka(B) virus, is produced by emryo fibroblasts of this strain and is devoid of leukemogenic activity. Although these viruses must share some genetic information, as is evidenced by their identical p30 internal coat proteins, for example, they are distinctively different in other important respects. Our objective is to characterize those RNA sequences unique to RadLV which might be responsible for its oncogenicity. The 50 to 70 S RNA from each viral preparation will be purified. After it has been ascertained that each isolated dimer species contain only one unique kind of monomer, "strong-stop" cDNA will be made against each of these RNAs and the products obtained will be compared. The viral genomes will be analyzed on denaturing agarose gel and their molecular weights determined. Each genome will then be separately eluted from the gel or transferred and fixed on diazobenzyloxymethyl paper and their sequences compared using cDNA-RNA hybridization. The cDNA probes will be made against each purified monomeric "35S" viral RNA species. Differences involving major portions of the genomes will be visualized and their positions mapped by making DNA-RNA heteroduplexes. Full-length DNA transcripts of a discrete viral genome will be hybridized to other viral RNAs, and the heteroduplexes formed will be studied by electron microscopy. Specific cDNA probes made using sequences unique to RadLV as templates will then be used to analyze for the presence and expression of oncogenic sequences in nonproducer radiation-induced C57BL/Ka thymic lymphoma cell lines, as well as in normal C57BL/Ka mouse thymus and bone marrow cells and in preneoplastic thymus cells harvested at various intervals after fractionated whole-body X-irradiation.